Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond

Background: Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse. Objective: To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice. Methods: Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid de carboxylase 65-k-Da isgform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173). Results: In group 1, at least I serum autoantibody (hut not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P1Q type or N type;). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (). In group 2, among 13 NMDA receptor IgG positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody pasitivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 grow) 1 encephalitis cases, p = 0.025). NMDA receptor 1gG was not detected in any healthy control subject. Conclusions: A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of comprehensive psychiatric, laboratory, radiologic, and electrophysiologic evaluations.